DD247221A1 - PROCESS FOR PREPARING 2,5-DISUBSTITUTED 1,3,4-THIADIAZONE DERIVATIVES WITH TRANS-CYCLOHEXANTRUCTURED FRAGMENTS - Google Patents

Abstract

The invention relates to a process for the preparation of 2,5-disubstituted 1,3,4-thiadiazole derivatives having trans-cyclohexane structure fragments of the structural formulas which are crystalline liquids and can therefore be used in electro-optical components. The aim of the invention is the preparation of crystalline-liquid 2,5-disubstituted 1,3,4-thiadiazole derivatives with trans-cyclohexanestructure fragments in high yields from 4-n-alkylcyclohexanecarboxylic acid hydrazides. It has been found that 2,5-disubstituted 1,3,4-thiadiazole derivatives with cyclohexanestructure fragments of 4-n-Alkylcyclohexancarbonsaeurehydraziden by reaction with substituted Benzoesaeurechloriden or Cyclohexancarbonsaeurechloriden and subsequent cyclization with P4S10 in an inert solvent at temperatures of 60 to 80C and Allow separation of the trans isomers by fractional crystallization. Formula I and II

Description

Explanation of the essence of the invention

The object of the invention is a process for the preparation of 2,5-disubstituted 1,3,4-thiadiazole derivatives with trans-cyclohexanestructure fragments.

It has been found that crystalline liquid 2,5-disubstituted 1,3,4-thiadiazole derivatives with trans-cyclohexanestructure fragments of the general formulas I and II by reacting 4-n-alkylcyclohexanecarboxylic acid hydrazides with substituted benzoic acid chlorides or substituted cyclohexanecarboxylic acid chlorides and subsequent cyclization with P ₄ Si ₀ in the presence of tertiary nitrogen bases, for example pyridine, in an inert solvent, preferably benzene, at reaction temperatures of 60 to 80 ⁰ C and reaction times of 4 to 6h can be produced.

By fractional crystallization from ethanol / butanol, the crystalline liquid trans-isomers obtainable in high purity from the crude product.

embodiments example 1

Preparation of 2- (4-n-butylphenyl) -5- (trans-4-n-hexylcyclohexyl) -1,3,4-thiadiazole 1 g of 2.26 g (0.01 mol) of 4-n-hexylcyclohexanecarboxylic acid hydrazide are added in 30 dissolved to 40ml benzene-pyridine mixture (ratio 7: 1) and cooled to a temperature between 0 and 5 ° C.

1.97 g (0.01 mol) of 4-n-butylbenzoyl chloride are slowly added dropwise in this temperature interval while stirring, and the mixture is stirred at this temperature for a further 45 to 60 minutes and then again at room temperature for 45 to 60 minutes. Thereafter, the Reaktinsgemisch is heated to about 80 to 85 ⁰ C within one hour and stirred for three hours at this temperature. After cooling to room temperature, the batch is mixed with 3.5 g P4S10. After cooling, the exothermic reaction is heated within one hour to 50 ⁰ C and stirred at this temperature for one hour.

The reaction mixture is then heated to 8O ⁰ C within 30 to 45 minutes and stirred under these conditions for 4 to 6 hours.

After cooling, 20 ml of ethanol are added, the solution poured into about 250 ml of ice-water and neutralized with aqueous 10% sodium hydroxide solution. The reaction product is filtered off, washed with plenty of water and dried. The crude product is recrystallized from much ethanol / butanol (ratio 8: 1) with the addition of activated carbon. The cis / trans isomers are separated by fractional crystallization because the trans isomers are solid while the liquid cis isomers are dissolved in the solvent.

Yield: 75% crude product

36% trans product

K58S _A 117N151I

Example 2

Preparation of 2- (3-bromo-4-n-nonyloxyphenyl) -5- (trans-4-n-butylcyclohexyl) -1,3,4-thiadiazole 1m 1.98g (0.01 mol) 4-n- Butylcyclohexancarbonsäurehydrazid be dissolved in 50ml benzene-pyridine mixture (ratio 7: 1) and cooled by ice cooling to 0 to 5 ⁰ C.

Thereafter, 3.62 g (0.01 mol) of З-ω-4-n-nonyloxybenzoyl chloride are added dropwise, and the mixture is stirred at this temperature for 90 minutes and then again at about 25.degree. C. to 30.degree. C. for 90 minutes. Then the reaction mixture erwärmt'man within one hour to about 8O ⁰ C and stirred for four hours at this temperature. After cooling to ambient temperature the mixture is treated with 3.5 g of P4S10, after the exothermic reaction is heated one hour at 50 ⁰ C and stirred at this temperature for about 90 minutes. Now the reaction mixture is heated to a temperature between 70 and 8O ⁰ C, and it is stirred for 4 to 6 hours within this temperature interval.

After cooling to room temperature, 25 ml of ethanol are added, the solution is poured into about 250 ml of ice water and neutralized with 10% sodium hydroxide solution. The product is filtered off, washed with 2 l of water (25 ° C), then dried and recrystallized from ethanol / butanol (ratio 6: 1) with activated charcoal. The separation of the cis / trans isomer mixture is carried out by fractional crystallization analogous to Example 1.

Yield: 80% crude product

40% trans product

K81S _A 113,5N117I

Example 3

Preparation of 2,5-bis (trans-4-n-butylcyclohexyl) -1,3,4-thiadiazole 2e

1.98 g (0.01 mol) of 4-n-butylcyclohexanecarboxylic acid hydrazide are dissolved in 50m! Benzen-pyridine mixture (ratio 8: 1 stirred and adjusted by ice cooling to a temperature of about 5 ⁰ C. Then added dropwise 2.02 g (0.01 mol) of 4-n-Butylcyclohexancarbonsäurechlorid, stirred for one hour at this temperature and Thereafter, the reaction mixture is heated to 80 ° C. within 30 minutes and stirred at this temperature for 6 hours After cooling to room temperature, 3.5 g of P ₄ SiO are added slowly.

After the exothermic reaction, the reaction mixture is heated over one hour to 5O ⁰ C and stirred for one hour at this temperature. It is then heated to 70 to 80 ° C and stirred at this temperature for about 6 hours. The mixture is cooled to room temperature and mixed with 30 ml of ethanol. The solution is poured into 300 ml of ice-water and neutralized with 10% sodium hydroxide solution. The crude product is filtered off, washed with plenty of water (25 ° C), dried and then recrystallized from ethanol / charcoal.

The separation of the cis / trans isomers is carried out by fractional crystallization analogously to Example 1.

Yield: 85% crude product

41% trans product K 65.5 S ₈ 1621

Example 4

Preparation of 2- (trans-4-n-butylcyclohexyl) -5- (trans-4-n-heptylcyclohexyl) -1,3,4-thiadiazole 2f 1.98 g (0.01 mol) of 4-n-butylcyclohexanecarboxylic acid hydrazide are dissolved in 100 ml Benzen-pyridine mixture (ratio 8: 1) stirred and cooled to a temperature between 10 ° C and 15 ⁰ C. Within this temperature interval, 2.45 g (0.01 mol) of 4-n-heptylcyclohexanecarboxylic acid chloride are slowly added dropwise and the mixture is stirred for 90 minutes at this temperature. Subsequently, the reaction mixture is heated to 80 ⁰ C and stirred for 5 hours at this temperature. After cooling to room temperature, the batch is mixed with 3.5 g of P ₄ S ₁ O. After the decay of the slightly exothermic reaction is heated within one hour to 6O ⁰ C and stirred at this temperature for 1.5 hours.

Then the reaction mixture is heated to 8O ⁰ C and stirred for 6 hours at this temperature. After cooling, about 30 ml of ethanol are added, the solution stirred into 300 ml of ice water and neutralized with 10% aqueous NaOH solution.

The crude product is filtered off, washed with plenty of cold water and taken up in diethyl ether. The ethereal solution is washed twice with 400 ml of cold water and then dried over Na ₂ SO ₄ . The diethyl ether is distilled off on a rotary evaporator and the crude product recrystallized from ethanol / activated carbon.

The separation of the cis / trans isomers is carried out by fractional crystallization.

Yield: 84% crude product

38% trans product K ¹⁾ S _B 174I

¹¹ Does not crystallize after 10 days at 30 ° C

 The following 2,5-disubstituted 1,3,4-thiadiazoles were synthesized analogously to Examples 1-4 (Table 1 and 2).

Table 1:

° ^H 2n + 1

R ¹

Sat.

1a 1b 1c 1d 1e 1f

C ₄ Hg- H- C ₄ Hg- H- C ₄ Hg- H- C ₄ Hg- H- C ₆ H ₁₃ - H- C ₆ H ₁₃ - H- C ₆ Hi ₃ - H- C ₆ H ₁₃ - H- C ₆ Hi ₃ - H- CN H- -CH H- C ₉ Hi ₉ O- Br

3 4 5 6 2 3 4 5 6 4 6 4

• 96 • 120 • 115 • 117

• 77 • 126 • 133 • 146 • 145

• 169 • 113.5

• 150 • 146 • 136

• 151

• 115 • 146 • 139

• 150

• 202 • 199 • 117

Table 2:

^С п ^Н 2p + 1

^C m ^H 2rn + 1

2a 2 2 • 118 2 B 3 3 • 126 • 143 2c 3 4 •1) • 159 2d 3 8th •1) • 172 2e 4 4 • 65.5 • 162 2f 4 7 •1) • 174 2g 5 5 • 49 • 180 2h 6 6 • 55 • 180 2І 6 8th •1) • 181

-144

¹¹ Does not crystallize after 10 days at -30 ° C.

Claims (1)

Invention claim: Process for the preparation of 2,5-disubstituted 1,3,4-thiadiazole derivatives with trans-cyclohexane structure fragments of the general formulas ^C m ^H 2rn + 1 where R ¹ = C _n H _{2n + 1} -, C _n H _{2n + 1} O-, CN R ² = Br, CH ₃ , CN
with n = Ibis 12 m = 1bis12 mean, from Carbonsäurehydraziden and cyclization with P ₄ S ₁₀ , characterized in that 4-n-Alkylcyclohexancarbonsäurehydrazide reacted with substituted Benzoesäurechloriden or Cyciohexancarbonsäurechloriden, then in an inert solvent, preferably in benzene, at 60 to 80 ⁰ C in the presence of tertiary nitrogen bases, ζ , As pyridine, cyclized and the trans isomers are separated by fractional crystallization from ethanol / butanol. Field of application of the invention The invention relates to a process for preparing 2,5-disubstituted 1,3,4-thiadizole derivatives having trans-cyclohexane structure fragments of the general formula ^C n ^H 2n + 1 ° n ^H 2n ₊₁ - < ^{H G} m ^H 2rn + 1 where R ¹ = C _n H _{2n +} , -, C _n H _{2n + 1} O-, CN R ² = Br, CH ₃ , CN
with n = Ibis 12 m = Ibis 12 means. The substances are crystalline-liquid and can therefore be used in electro-optical components. Characteristic of the known technical solutions The most important syntheses subst. 1,3,4-thiadiazoles are based on a two-nitrogen fragment as starting compounds. Stolle describes the reaction of dibenzoyl hydrazides with P ₄ S ₁₀ at 250 ° C by dry heating. (R.Stolle et al., J. prakt. Chemistry 2 69,158 [1904], 70,424 [1904]). Another method is the thioacylation of a thiohydrazide (K. A. Jansen, C. Petersen, Acta, ex. Scand. 15,1124 [1961]) or starting from thiobenzoic acid hydrazides by reaction with imidic acid ester hydrochlorides and by oxidation of thiobenzhydrazones of benzaldehyde with iron-III chloride or potassium persulfate (H. Weidinger, J. Kranz, Chem. Ber. 96, 1059 [1963] , B. Holmberg, Ark. Kemi, Mineral, o. Geol., 25, A, No. 18 [1947], Ark. Kemi, 9, 65 [1956]). Another method is the reaction of aldehyde, hydrazine hydrate and sulfur in an inert solvent at 60-120 ⁰ C, but only symmetrical 1,3,4-thiadiazoles and - this is true for all previously enumerated methods - poor yields yields (H. Hagen, F.Becke, Ger.2.132.019 Jan. [1973] CA 78 97665). A much cheaper alternative is the reaction of Ν, Ν'-dibenzoylhydrazides in the presence of a tertiary nitrogen base, ζ. As pyridine, with P ₄ Si ₀ under reflux conditions. The advantages of this reaction are the preparation of unsymmetrical 1,3,4-thiadiazoles and the possibility of carrying out the acylation of the carboxylic acid hydrazide and the subsequent cyclization as a one-pot reaction. (AE Siegrist, E. Maeder, M. Dünneberger, P. Liecht, CH-P 411,906, CH-P 390,924, CH-P 426,848, C.A. 68.690029 [1968]). Patented is the preparation of 1,3,4-thiadiazoles from aliphatic, araliphatic, heterocyclic or preferably aromatic acylhydrazides. However, this method is not suitable for the preparation of cyclohexyl-substituted thiadiazoles, since only dark brown oils are obtained from which the trans isomers can not be isolated. Object of the invention The object of the invention is the preparation of 2,5-disubstituted 1,3,4-thiadiazole derivatives with trans-cyclohexanestructure fragments in good yields from readily available starting materials.